Maternal underweight and obesity and risk of orofacial clefts in a large international consortium of population-based studies

Kutbi, Hebah A.; Wehby, George L.; Uribe, Lina M. Moreno; Romitti, Paul A.; Carmichael, Suzan L.; Shaw, Gary M.; Olshan, Andrew F.; DeRoo, Lisa A.; Rasmussen, Sonja A.; Murray, Jeffrey C.; Wilcox, Allen J.; Lie, Rolv Terje; Munger, Ronald G.

doi:10.1093/ije/dyw035

Cited by 26 publications

(38 citation statements)

References 38 publications

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“…Among cases, 1134 had cleft lip only, 2078 had cleft lip with palate, and 1723 had cleft palate only. As reported in prior studies (1, 3), smoking, underweight, and obesity rates were higher among cases than controls.…”

Section: Resultssupporting

confidence: 76%

“…We did not control for diabetes because it can be a consequence of obesity. Furthermore, prior work has shown that it did not meaningfully account for the associations of BMI with risk of oral clefts (3). …”

Section: Methodsmentioning

confidence: 99%

“…The model also adjusted for any maternal alcohol consumption and use of folic-acid-containing supplements in the first trimester, and age (≤18, 19–25, 26–30, 31–35, and ≥36 years), an indicator for low maternal education (incomplete high school versus higher education), and dummy variables representing the 6 contributing studies. These study-specific fixed effects account for differences among the study populations in oral cleft risk factors, prevalence, time effects, and case-to-control ratios (1, 3, 21). These fixed effects, as well as the balancing of cases and controls by year of birth within each study, ensured that time is not a confounder in the pooled analysis.…”

Section: Methodsmentioning

confidence: 99%

“…Another consistent risk factor is BMI. Obese mothers have elevated risks of children with oral clefts compared with normal-weight mothers (3). …”

Section: Introductionmentioning

confidence: 99%

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Interaction between smoking and body mass index and risk of oral clefts

Wehby

Uribe

Wilcox

et al. 2017

Annals of Epidemiology

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Purpose To examine maternal smoking and body mass index (BMI) interactions in contributing to risk of oral clefts. Methods We studied 4935 cases and 10,557 controls from 6 population-based studies and estimated a pooled logistic regression of individual-level data, controlling for study fixed effects and individual-level risk factors. Results We found a significant negative smoking-BMI interaction, with cleft risk with smoking generally declining with higher BMI. For all clefts combined, the OR for smoking was 1.61 (95% CI: 1.39–1.86) at BMI 17 (underweight), 1.47 (95% CI: 1.34–1.62) at BMI 22 (normal weight), 1.35 (95% CI: 1.22–1.48) at BMI 27 (overweight), 1.21 (95% CI: 1.04–1.41) at BMI 33 (obese), and 1.13 (95% CI: 0.92–1.38) at BMI 37 (very obese). A negative interaction was also observed for isolated clefts and across cleft types but was more pronounced for cleft lip only and cleft palate only. Conclusions Our findings suggest that the risk of oral clefts associated with maternal smoking is largest among underweight mothers, although the smoking-BMI interaction is strongest for cleft lip only and cleft palate only. BMI was not protective for the effects of smoking; a clinically relevant increase in smoking-related cleft risk was still present among heavier women.

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Section: Resultssupporting

confidence: 76%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

“…Another consistent risk factor is BMI. Obese mothers have elevated risks of children with oral clefts compared with normal-weight mothers (3). …”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Interaction between smoking and body mass index and risk of oral clefts

Wehby

Uribe

Wilcox

et al. 2017

Annals of Epidemiology

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“…Moreover, it was suggested that both overweight and underweight interfere with the process of palatal development [15]. This could be linked to maternal nutritional deficiencies and imbalanced dietary patterns during pregnancy which have been strongly associated with the development of OC.…”

Section: Etiologymentioning

confidence: 99%

Non-Syndromic Oral Clefts: A Glimpse on Environmental Risk Factors- A Mini-Review

fadl¹

2017

JPNC

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Association between maternal body mass index and congenital anomalies: A case‐control study in Tuscany (Italy)

Mezzasalma

Santoro

Coi

et al. 2021

Birth Defects Research

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Objective To investigate the relationship between prepregnancy maternal body mass index (BMI) and congenital anomalies (CAs). Design Case‐control study on data collected by the registry of CAs of Tuscany (Italy) and birth certificates from 2005 to 2017. Main exposure Maternal prepregnancy BMI. Main outcome measures Any major CAs and groups of organ‐specific anomalies. Odds ratios (ORs) were estimated using logistic regression models adjusted for maternal factors. Results Maternal BMI ≥25 was significantly associated with all nervous system anomalies (OR = 1.61, 95% confidence interval [95% CI] 1.13–2.29) and with neural tube defects (OR = 2.03, 95% CI 1.00–4.12); maternal underweight was significantly associated with orofacial clefts (OR = 1.67, 95% CI 1.12–2.48). After stratification by education, in the low education group, mothers with BMI ≥25 had an increased risk of nervous system anomalies (OR = 2.19, 95% CI 1.01–4.76), whereas underweight mothers had an increased risk of nervous system anomalies (OR = 3.89, 95% CI 1.44–10.53), orofacial clefts (OR = 2.59, 95% CI 1.24–5.42), and urinary anomalies (OR = 1.74, 95% CI 1.07–2.82). In the medium/high education group, the only significantly increased risk was found in mothers with BMI ≥25 for nervous system anomalies (OR = 1.50, 95% CI 1.00–2.25). Conclusion Main results have shown a positive association of maternal BMI ≥25 with nervous system anomalies and maternal underweight with orofacial clefts. The study has also evidenced the impact of social status and provided clues to the role of maternal ethnic background.

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Maternal underweight and obesity and risk of orofacial clefts in a large international consortium of population-based studies

Cited by 26 publications

References 38 publications

Interaction between smoking and body mass index and risk of oral clefts

Interaction between smoking and body mass index and risk of oral clefts

Non-Syndromic Oral Clefts: A Glimpse on Environmental Risk Factors- A Mini-Review

Association between maternal body mass index and congenital anomalies: A case‐control study in Tuscany (Italy)

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